Case 1: Diabetic neuropathic foot arthropathy (Charcot foot)

By Stephanie V. Sherman, MD

The patient

A 37-year-old woman presented with four weeks of progressive pain, redness, and swelling
in her left foot. She works and spends most of the day on her feet but had not experienced
recent foot trauma or ulcers. She had no fevers, chills, arthritis, or myalgias but
did have painful paresthesias in both feet. Her medical history included hypertension
and poorly controlled type 2 diabetes (HbA1c, 13%).

Plain X-ray of left foot showing erosion of the proximal second metatarsal and medial
aspect of proximal third metatarsal shaft and base (circle). The image also shows
lateral displacement of the metatarsals along the tarsal bones (arrow).

On presentation, her temperature was 98.8 °F, her blood pressure was 149/104
mm Hg, and her heart rate was 97 beats/min. Her left foot had a flat arch with lateral
deviation of the forefoot. The foot was warm, red, and swollen when compared to the
right. There was no tenderness, ulceration, or limited range of motion at the ankle.
She had onychomycosis and decreased proprioception. Labs showed a normal white blood
cell count, erythrocyte sedimentation rate (ESR) of 26 mm/h (normal <20 mm/h),
high-sensitivity C-reactive protein level of 0.478 mg/dL (normal <0.3 mg/dL),
and negative blood cultures. Plain radiography of the foot showed lateral displacement
of the metatarsals with erosion of the proximal second and third metatarsals, concerning
for osteomyelitis (Figure 1). An MRI showed increased T2 signal in all tarsal and metatarsal bones with associated
soft-tissue edema, also consistent with osteomyelitis. The patient declined immediate
foot amputation and instead underwent bone biopsy, which showed normal bone with negative
cultures. Ultimately, she was treated conservatively with immobilization and an off-loading
shoe.

The diagnosis

Diabetic neuropathic foot arthropathy (Charcot foot) is a noninfectious complication
of diabetic neuropathy in which loss of proprioception results in changes in weight-bearing
that lead to chronic, progressive bony destruction. Charcot foot can present acutely
with warmth, erythema, and induration, thus mimicking common conditions such as soft-tissue
infection, septic arthritis, gout, or osteomyelitis. On physical exam, Charcot foot
often presents with soft-tissue inflammation and distorted bony architecture such
as metatarsal deviation and collapsed arch. Pinprick and position sensation are typically
reduced while pulses are preserved. Foot ulcers may be present, though their absence
significantly lowers the likelihood of osteomyelitis as the cause of bone destruction.
In Charcot foot, laboratory markers of inflammation, such as peripheral white blood
cell count and ESR, are typically normal.

Although imaging is commonly used to work up diabetic foot symptoms, results may not
easily differentiate Charcot foot from osteomyelitis. Both Charcot foot and osteomyelitis
can lead to periosteal reactions and bone erosion on plain radiograph; on MRI, both
diagnoses are associated with abnormal bone marrow signal, cortical disruption, and
adjacent soft-tissue inflammation. Radiographic features that support the diagnosis
of Charcot foot include involvement of the midfoot (instead of toe, forefoot, or heel
in osteomyelitis) and presence of joint subluxations or dislocations. If the diagnosis
remains equivocal after consultation with a radiologist, a bone biopsy can be performed
to rule out osteomyelitis, although it is not required to diagnose Charcot foot.

Pearls

Charcot foot can be challenging to differentiate from osteomyelitis clinically and
on commonly ordered imaging studies; normal inflammatory markers and joint or arch
deformities can help distinguish this condition from other diabetic foot complications.

Case 2: Acute bacterial prostatitis

By Zaven Sargsyan, MD

The patient

A 61-year-old man with type 2 diabetes was admitted with two days of hematuria and
fever. Ten days prior to admission, he was treated for new urinary retention, which
was attributed to prostatic hypertrophy and the use of diphenhydramine for allergies.
An indwelling urinary catheter was placed, and he was started on tamsulosin. One week
later, he began to experience malaise, chills, dysuria, and intermittent bleeding
into his urinary catheter bag. On examination, he was febrile, tachycardic, and tender
over the left lower and suprapubic abdomen. There was no costovertebral angle tenderness.
His catheter was draining cloudy, pink-tinged urine. The rectal exam was deferred.
Treatment with intravenous fluids and cephalosporin antibiotics was initiated. Serum
laboratory values were notable for a white blood cell count of 21,000 cells/µL.
Urinalysis showed 148 white blood cells and 89 red blood cells per high-power field,
but no nitrites. The urine culture grew Serratia marcescens susceptible to both cephalosporins and fluoroquinolones; blood cultures were sterile.
Over the next three days, while receiving a cephalosporin antibiotic, the patient's
leukocytosis and tachycardia improved, but he continued to have malaise and intermittent
fevers. A CT of the abdomen was performed, showing no nephrolithiasis, unremarkable
kidneys, and a moderately enlarged prostate with heterogeneous contrast enhancement.
The serum prostate-specific antigen (PSA) level was elevated at 76 ng/mL (normal <4
ng/mL). Antibiotic therapy was changed to ciprofloxacin, after which the patient rapidly
defervesced. After a 6-week course of antibiotics was completed, the PSA normalized.

The diagnosis

Acute bacterial prostatitis is rare and a challenge to distinguish from a simple urinary
tract infection. Enteric gram-negative bacilli are the most common culprits and are
thought to infiltrate the gland through intraprostatic urinary reflux. Major risk
factors include anatomic abnormalities such as urinary retention or instrumentation
and immunocompromised states such as diabetes mellitus. Prostatitis should be suspected
in men with urinary tract infections who exhibit signs of sepsis but do not have apparent
pyelonephritis or obstructive nephrolithiasis. Acute urinary retention, transient
elevation in PSA, and gland enlargement and hyperemia on imaging can support the diagnosis.
A digital rectal exam may also be helpful by demonstrating “bogginess”
and tenderness of the gland, but vigorous massage should be avoided, as it may precipitate
bacteremia.

Recognizing prostatic involvement in a lower urinary tract infection is important
for several reasons. Acute prostatitis is potentially life-threatening, resulting
in bacteremia in up to 25% of cases. Inadequate response to antibiotics can necessitate
surgical drainage of prostatic abscesses. The treatment of bacterial prostatitis requires
appropriate antibiotic selection for prostatic tissue penetration. Fluoroquinolones
and trimethoprim-sulfamethoxazole have better penetration than many beta-lactams or
carbapenems and are favored by most experts when culture data are available. In the
acutely ill patient, however, the initial antibiotic choice should be informed by
susceptibility patterns of Enterobacteriaceae locally or from the individual's past
specimens.

Pearls

Consider acute bacterial prostatitis when urinary tract infections lead to sepsis
or acute urinary retention in men, particularly in those with prostatic hypertrophy
and diabetes mellitus.

Fluoroquinolones and trimethoprim-sulfamethoxazole have superior prostatic penetration
and should be used to treat bacterial prostatitis, especially if culture data and
sensitivity information are available.

Biopsies revealed noncaseating granulomas (Figure 3) with negative acid-fast bacilli (AFB) stain and culture. Repeat IGRA testing was
positive. Therapy for Mycobacterium tuberculosis with rifampin, isoniazid, pyrazinamide, and ethambutol (RIPE) was initiated, but the
patient was ultimately lost to follow-up.

The diagnosis

Tuberculous peritonitis (TBP) accounts for less than 1% of all forms of Mycobacterium tuberculosis (MTB) infection, but it is the most common form of gastrointestinal MTB. Infection
occurs most commonly due to reactivation of latent tuberculosis peritoneal foci that
were established during primary lung infection via hematogenous spread. Risk factors
include residence in endemic MTB regions, alcoholic liver disease, peritoneal dialysis,
anti-tumor necrosis factor drug therapy, diabetes, and HIV infection. TBP presents
with nonspecific symptoms including fevers, weight loss, anorexia, nausea, vomiting,
abdominal pain, diarrhea, constipation, and abdominal swelling. Portal vein thrombosis
is a rare but documented manifestation. Concurrent lung involvement may be present,
although 80% of gastrointestinal MTB infection occurs in the absence of active pulmonary
disease.

The diagnosis of TBP is challenging given its insidious onset and variable presentation;
TBP should, however, be considered in all patients with lymphocytic ascites with a
low SAAG. This young woman's elevated CA-125 level made ovarian cancer a consideration,
but this marker can also be elevated in TBP and thus often confounds the diagnosis.
TB studies and laparoscopy form the basis of diagnosis. While the purified protein
derivative (PPD) test is not helpful in the diagnosis of active MTB infection, IGRA
testing has greater than 90% sensitivity and specificity in the diagnosis of acute
TBP. Ascitic AFB smear testing is positive in fewer than 3% of fluid samples. While
polymerase chain testing for MTB is only useful for AFB smear-positive ascites samples,
fluid cultures are positive in approximately one-third of cases. Elevated adenosine
deaminase (ADA) levels in ascitic fluid additionally aid in diagnosis, given high
sensitivity (93%) and specificity (96%). Laparoscopy also has excellent sensitivity
(93%) and specificity (98%) when macroscopic appearance and histology findings are
combined. Although MTB is classically associated with caseating granulomas, noncaseating
granulomas can also be seen in biopsy of infected tissue.

Pearls

Gastrointestinal tuberculosis infection, specifically TBP, should be considered in
the differential diagnosis in patients with unexplained low SAAG ascites and risk
factors for MTB infection.

Adenosine deaminase levels in ascites may assist in diagnosis, but laparoscopy with
tissue biopsy should be considered in all patients with possible TBP to avoid delays
in diagnosis and treatment.

The patient

Asymmetric swelling of the right lower extremity with erythema.

A 61-year-old woman presented to her outpatient physician with erythema and swelling
of the right lower leg. She reported no fever, chills, trauma, travel, prolonged immobilization,
chest pain, shortness of breath, paroxysmal nocturnal dyspnea, or abdominal swelling.
Outpatient evaluation consisted of a lower-extremity ultrasound, which was negative
for deep venous thrombosis, and a CT of the extremity that showed nonspecific soft-tissue
swelling. Despite a course of antibiotics for presumed cellulitis, the erythema worsened,
and she was admitted for antibiotic “failure” and intravenous therapy.
On hospital presentation, she had normal vital signs. Her right leg was swollen and
erythematous with increased thigh girth compared to the left; her left leg appeared
normal (Figure 4). Nontender right inguinal lymphadenopathy was present.

Further history revealed a diagnosis of stage I uterine adenocarcinoma six years prior,
treated with hysterectomy and bilateral salpingo-oophorectomy. A CT of the pelvis
showed significant right iliac chain lymphadenopathy causing right external iliac
vein compression (Figure 5). Lymph node core needle biopsy revealed metastatic poorly differentiated carcinoma.
She underwent stenting of the right external iliac vein and peritoneal debulking,
which revealed endometrial adenocarcinoma with lymphovascular invasion.

The diagnosis

This patient's unilateral leg swelling resulted from malignant lymph nodes compressing
the external iliac vein in the setting of uterine adenocarcinoma recurrence. Endometrial
cancer is the most common gynecologic malignancy in the United States with more than
60,000 new cases per year. It has an approximate 15% overall rate of relapse, most
often within three years of initial diagnosis. Presenting signs of localized relapse
include vaginal bleeding, pelvic pain, and constitutional symptoms. Usual sites of
recurrence are the vagina, pelvic and para-aortic lymph nodes, peritoneum, and lung.
In the pelvic region, lymphangitic spread is most commonly seen to the external iliac
lymph nodes followed by obturator and common iliac nodes. While lower-extremity swelling
from venous obstruction in metastatic gynecological cancers has been described, this
type of swelling may be mistakenly attributed to secondary lymphedema. Venous obstruction
can be amenable to stent placement, which can alleviate the obstruction, increase
mobility, and improve quality of life.

Unilateral lower-extremity edema warrants further evaluation of the underlying cause,
with consideration of soft-tissue, vascular, and lymphatic pathologies. Soft-tissue
causes of unilateral edema include infections and compartment syndrome. Disruptions
in the venous drainage system from deep venous thrombosis or prior vein stripping
can also result in unilateral edema. Unilateral edema secondary to lymphatic obstruction
can be seen with surgery, malignancy, radiation-induced scarring, recurrent infections,
lymphatic hypoplasia, and filariasis. Bilateral swelling may be asymmetric due to
physiologic compression of the left iliac vein by the right iliac artery or prior
vascular or lymphatic injury to the lower extremity.

Pearls

Inguinal lymphadenopathy may be the initial presentation for an occult malignancy,
especially with gynecologic cancers that develop lymphangitic spread to the external
iliac, obturator, and common iliac lymph nodes.

Unilateral lower-extremity edema has a variety of causes, including venous obstruction,
and may potentially be alleviated by stent placement.

Drs. Sherman, Sargsyan, Sajja, Khawaja, and Dangayach are affiliated with Baylor College
of Medicine in Houston.

Clostridium difficile enteritis

By Sarah Bowen, PharmD, and James Griffith, MD, FACP

The patient

A 73-year-old woman presented from her nursing home for evaluation of a five-day history
of increased lethargy. Her medical history included chronic kidney disease, recurrent
urinary tract infections (UTIs), congestive heart failure, and numerous recent hospitalizations
for complications of abdominal surgeries. Her surgical history was significant for
several recent bowel surgeries, including an abdominal colectomy one year prior. On
presentation, vital signs were stable and she was afebrile. Urinalysis was consistent
with a UTI, and she was admitted for intravenous antibiotic therapy. On the third
hospital day, copious ileostomy output was noted and her leukocyte count increased
from 12,600 cells/μL to 56,000 cells/μL. Clostridium difficile toxin testing was positive. The patient was started on oral vancomycin and intravenous
metronidazole due to the severity of disease. Her course was complicated by progressive
shock requiring ICU transfer. After an extended hospital stay with treatments for
other suspected infections and progressive deterioration, her family eventually decided
to pursue comfort care. The patient was discharged home with hospice services.

The diagnosis

C. difficile is commonly recognized as a cause of infectious colitis but has been increasingly
acknowledged as a cause of small-bowel infection. There have been more than 60 cases
of C. difficile enteritis (CDE) reported in the literature since 1980, most after 2000. CDE is more
common after colectomy and in patients with inflammatory bowel disease. CDE presents
with signs and symptoms similar to C. difficile colitis, including leukocytosis, diarrhea (or increased ileostomy output), fever,
and abdominal pain. The risk factors are also similar to those of C. difficile colitis, including antibiotic use, hospitalizations, immunocompromise, and chronic
kidney disease. Mortality with CDE appears to be higher than in C. difficile colitis, as high as 60% in some reports. There are no specific treatment guidelines
or diagnostic criteria for CDE, but current literature suggests using standard C. difficile treatment for similar duration. Maintaining a high index of suspicion for CDE in postcolectomy
patients with increased ileostomy output can lead to earlier recognition and treatment
of CDE, potentially decreasing morbidity and mortality in these patients.

Pearls

Risk factors for CDE include inflammatory bowel disease and colectomy.

CDE is less common than C. difficile colitis, but data suggest a potentially higher mortality of up to 60%.

Dr. Bowen is a fourth-year medical student and Dr. Griffith is a professor of internal
medicine and psychiatry at West Virginia University, Charleston Division.

ACP Hospitalist provides news and information for hospitalists, covering the major issues in the field. All published material, which is covered by copyright, represents the views of the contributor and does not reflect the opinion of the American College of Physicians or any other institution unless clearly stated.